GYS2

Chr 12AR

glycogen synthase 2

NCBI Gene: 2998ENSG00000111713UniProt: P54840

Liver glycogen synthase catalyzes the rate-limiting step in glycogen synthesis by transferring glucose from UDP-glucose to growing glycogen chains. Mutations cause glycogen storage disease type 0, characterized by early childhood fasting hypoglycemia with decreased liver glycogen content. This condition follows autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Glycogen storage disease 0, liverMIM #240600
AR
0
Active trials
19
Pubs (1 yr)
150
P/LP submissions
9%
P/LP missense
1.13
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— GYS2
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Gene-Disease Validity (ClinGen)
glycogen storage disorder due to hepatic glycogen synthase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
90 unique Pathogenic / Likely Pathogenic· 159 VUS of 427 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 0.89
OE 0.85 (0.65–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.14Z-score
OE missense 0.98 (0.90–1.07)
374 obs / 381.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.85 (0.65–1.13)
0≤0.351.4
Missense OE0.98 (0.90–1.07)
0≤0.61.4
Synonymous OE1.19
0≤1.21.6
LoF obs/exp: 36 / 42.2Missense obs/exp: 374 / 381.6Syn Z: -1.79
DN
0.6358th %ile
GOF
0.4283th %ile
LOF
0.4332th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
LOF28% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

427 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic33
VUS159
Likely Benign101
Benign54
Conflicting19
57
Pathogenic
33
Likely Pathogenic
159
VUS
101
Likely Benign
54
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
49
0
57
Likely Pathogenic
18
7
8
0
33
VUS
3
121
27
8
159
Likely Benign
0
10
42
49
101
Benign
0
7
42
5
54
Conflicting
—19
Total2814616862423

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GYS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
A patient with glycogen storage disease type 0 and a novel sequence variant in GYS2: a case report and literature review.
Arko JJ et al.·J Int Med Res
2020Review
ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity.
Dong F et al.·Int J Biol Sci
2023
PPP1R3B Suppresses Atherosclerosis by Promoting the M2 Polarization of Macrophages Through Glycogen Metabolic Reprogramming.
Shen L et al.·Adv Sci (Weinh)
2025
A GYS2/p53 Negative Feedback Loop Restricts Tumor Growth in HBV-Related Hepatocellular Carcinoma.
Chen SL et al.·Cancer Res
2019
The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.
Chen W et al.·Cardiovasc Diabetol
2024Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Single nucleotide polymorphisms of GYS2 gene and its association with milk production traits of dairy cows.
Ye W et al.·Anim Biotechnol
2024Open Access
Identification of BMAL1-Regulated circadian genes in mouse liver and their potential association with hepatocellular carcinoma: Gys2 and Upp2 as promising candidates.
Zhao H et al.·Biochem Biophys Res Commun
2024Functional
Whole-Exome sequencing identifies GYS2 biallelic variants in individuals with suspected epilepsy.
Ilyas M et al.·Seizure
2024
[Glycogen storage syndrome type 0 caused by GYS2 gene variation and phenotypic differences between two siblings].
Liao Y et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2021
Lupin protein isolate improves insulin sensitivity and steatohepatitis in vivo and modulates the expression of the Fasn, Gys2, and Gsk3b genes.
Soto-Luna IC et al.·Food Sci Nutr
2021Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients